tbuckley/cabot-search huggingface dataset:
A comparative study of unmet information needs of patients with lymphoma and CLL: North America and Europe.
Authors: Olufunmilayo (Funmi) Bamigbola, Lorna Warwick
Journal: Journal of Clinical Oncology (2022)

12135 Background: Informed patients are consistently associated with better outcomes and overall patient experiences. However, there are still unknowns about the information needs of patients. This study uses the Lymphoma Coalition (LC) 2020 Global Patient Survey (GPS) on Lymphomas and CLL to describe the differences in the unmet information needs among patients with lymphoma and CLL in North America and Europe. Methods: Globally, 9,179 patients from 90+ countries took part in the LC 2020 GPS. The countries were grouped into regions, and the North American (NA) (n=1543) and European (EU) (n=4343) regions were used for this analysis (Table). The demographics of the regions were examined, and univariate, bivariate and multivariate analyses of questions relating to patients’ information needs, were performed in IBM SPSS v27. Results: When compared, the regions differed significantly in patients’ age distribution, lymphoma subtype, highest educational level completed, and area of residence. The top three areas of unmet information need for patients with lymphoma and CLL in both regions were: diagnosis and what it means, treatment options, and side effects from treatment. Compared to patients in the EU, patients in NA were 27% more likely to need more information about treatment options, 51% more likely to need more information about support for self-care, and 18% less likely to need more information about their diagnosis and what it means. These differences were statistically significant (Table). Patients from NA were 26% more likely to report that they had no informational needs compared to patients from EU (p=0.02) (Table). There was no significant difference between patients in both regions in their need for more information in the following areas: psychological support, support for their families, side effects from treatment and fertility (Table). Conclusions: Regardless of region, patients with lymphoma need more information about certain areas of their care than is currently provided. LC advocates for increased access to appropriate and adequate medical information for patients, and that this information be contextualized to the patient’s needs.[Table: see text]
NANORAY-312: A phase III pivotal study of NBTXR3 activated by investigator’s choice of radiotherapy alone or radiotherapy in combination with cetuximab for platinum-based chemotherapy-ineligible elderly patients with locally advanced head and neck squamous cell carcinoma.
Authors: Christophe Le Tourneau, Caroline Hoffmann, Zoltan Takacsi-Nagy, Xavier Liem, Sébastien Salas, Anais Debard, Laetitia Finzi, Leonard A Farber, Miranda Gogishvili, Giorgi Kristesashvili, Tamta Makharadze, Sue S. Yom
Journal: Journal of Clinical Oncology (2022)

TPS6110 Background: Elderly patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC) are largely underrepresented in clinical trials (CT). Broad access to CTs in this population is challenging due to an increased prevalence of comorbidities and ageing-related conditions. However, as population-age increases, more and more elderly patients are diagnosed with LA-HNSCC although many are not eligible to receive standard cisplatin-based concurrent chemoradiation (CRT). CRT-related toxicities, treatment burden and compliance are a concern. NBTXR3, a first-in-class radioenhancer, composed of functionalized hafnium oxide nanoparticles, is administered by one-time intratumoral injection and activated by radiotherapy (RT). NBTXR3 is designed to locally amplify the tumor-killing effect of radiotherapy without additional toxicity to surrounding healthy tissue. NBTXR3 has been shown to prime the adaptive immune response in cancer models. NBTXR3 obtained EU marketing approval in preoperative treatment of locally advanced soft tissue sarcomas. In a Phase I trial of NBTXR3 + RT alone in elderly LA-HNSCC patients, the combination was shown to be safe and an Objective Response Rate (ORR) of 85.4% and CRR of 51.2% was reported at ASTRO 2021. A pivotal randomized phase III study was initiated and is now recruiting. Methods: NANORAY-312 [NCT04892173] is a global, open-label, randomized (1:1), 2-arm, Investigator's choice Phase III (Pivotal Stage) study to investigate the efficacy and safety of NBTXR3/RT±cetuximab versus RT±cetuximab in treatment-naïve, platinum-ineligible, elderly patients with LA-HNSCC. 500 patients will be enrolled. Eligible patients are ≥65 years with at least one measurable (RECIST 1.1) biopsy-confirmed T3-4 (AJCC v8) SCC of the oral cavity, oropharynx, hypopharynx, or supraglottic larynx which is amenable for intratumoral injection. For patients with oropharyngeal cancer, human papilloma virus (HPV) status must be known. In addition to the primary tumor, a single accessible LN in the neck is eligible for intranodal injection. The primary objective is PFS. The key secondary endpoint is OS. Other secondary endpoints include ORR, safety and tolerability and quality of life. Enrollment began in January 2022 and is ongoing. Clinical trial information: NCT04892173.
Phase 2, randomized, double-blind trial of EC-18 versus placebo to mitigate the development and time course of oral mucositis from concomitant chemoradiation for head and neck cancer.
Authors: Christina Henson, Daniel Clayburgh, Arielle Shebay Lee, Deborah J.L. Wong, Mahesh R. Kudrimoti, Douglas Adkins, Steve P. Lee, Noah Kalman, Peter John Oppelt, Krishna A. Rao, Ji Sun Park, Sookyung Oh, Koeun Kim, Sun Young Yoon, Ki Young Sohn, Stephen T. Sonis
Journal: Journal of Clinical Oncology (2022)

12106 Background: Oral mucositis (OM) is a debilitating side effect of concomitant chemoradiotherapy (CRT) for head and neck cancer (HNC). EC-18 may effectively mitigate OM by minimizing the CRT-induced innate immune response. This Phase II, 2-stage trial evaluated safety, tolerability, and efficacy of EC-18 in reducing the duration, incidence, and trajectory of severe OM (SOM) in HNC patients. Methods: Patients (n = 105) with pathologically confirmed oral cavity, oropharynx, hypopharynx, or nasopharynx squamous cell cancers who received intensity-modulated radiation therapy (IMRT; with ≥ 55 Gy on ≥ 2 oral sites) and weekly or tri-weekly cisplatin were studied. In Stage 1, 24 patients were randomized (n = 6 per arm) to receive 500, 1000, or 2000 mg of EC-18, or placebo. Following independent Data Safety Monitoring Board review, 81 patients in Stage 2 received EC-18 2000 mg (n = 41) or placebo (n = 40) throughout CRT. WHO OM grade was assessed twice weekly during IMRT and then once weekly for up to 6 weeks post-IMRT. The primary efficacy endpoint was duration of SOM during the active and short-term follow-up (STFU) periods in the compliant per-protocol population (PP). Much of Stage 2 was conducted during peak periods of the COVID-19 pandemic which measurably impacted patient compliance relative to test medication dosing and planned radiation. Consequently, to assess efficacy most accurately, the PP population was analyzed (with at least 4 weeks of study drug dosing, minimum cumulative radiation of 55 Gy, 80% study drug compliance in the first 28 days of dosing, and without using not-allowed-therapy). Results: Patient demographics and baseline characteristics were balanced between groups. Adverse events (AEs) were comparable amongst cohorts without drug-related severe AEs. In the PP, the median duration of SOM from baseline through STFU was 0 day in the EC-18 group (n = 22) v 13.5 days in the placebo group (n = 20). SOM incidence through STFU (45.5% v 70%) and opioid use (time to onset: 32.3 v 26.0 days; and duration: 32.8 v 37.5 days) favored EC-18 v placebo. Results of the covariates analyses suggested that EC-18 favorably impacted SOM incidence in patients who experienced SOM treated with weekly low-dose cisplatin (n = 26; 37.5% v placebo 70.0%) and HPV+ tumors (n = 29; 35.3% v placebo 66.7%; Table). One-year long-term follow-up for tumor outcomes is ongoing. Conclusions: EC-18 safely mitigated the development and the time course of SOM in CRT-treated HNC patients. In addition, EC-18 may provide substantial benefits to subpopulations of HPV + HNC patients treated with low dose cisplatin. Clinical trial information: NCT03200340. [Table: see text]
Imatinib may not be the best choice for planning TFR in CML patients.
Authors: Amal S. Alabdulwahab, Hussein E.G. EL sayed, Mohamed A. Sherisher, Khalofa A. Alghamdi
Journal: Journal of Clinical Oncology (2022)

e19059 Background: Treatment of chronic myeloid leukemia had been revolutionized by the use of Tyrosine kinase inhibitors. Recently, the strategy of treatment free remission had been introduced to ameliorate toxicity and reduce financial burden beside allowing patients who now have similar survival to normal people to achieve some goals as childbearing. Aim of this study: to check the suitability of imatinib as a first line treatment in potential patients in whom treatment free remission will be an ultimate goal. Methods: This study included patients with chronic myeloid leukemia, chronic phase who were treated in King Abdulla Medical city in the period between 2011 and end of 2019. Initial diagnosis was done by bone marrow, cytogenetics, molecular testing for BCR/ABL. Quantitative estimation of BCR-ABL1 was done on peripheral blood every 3 months to follow response which was assessed according to ELN criteria for follow up. Results: 140 patients were included in this study who received imatinib as first line therapy. The male to female ratio was 1.1 and the median age was 42 Y. 17 patients (12.1 %) were &gt; 60 Y at start of treatment. The majority of patients were considered low risk (70.2%) as by EUTOS risk score. Breakpoint region was e13/a2 in 39.3%, e14/a2 in 38.3% and unknown in 22.7% of patients. 62% of patients were compliant with treatment. At the time of analysis, 79 patients (56%) remained on imatinib. 51/140 (36%) stopped it due to failure, 11 due to intolerance (7.9%). Favorable molecular responses were achieved in 67.4%, 53.9% and 50% at 3,6,12 months respectively. Compliance and risk scores were significantly affecting these responses. 54/70 (77%) of those who achieved MMR at 12 months achieved a deep molecular response (M 4 , M 4.5 ) after a median period of 36 m. 40 patients (57%,74%) of those who achieved MMR, DMR respectively developed DMR lasting for more than 2 years (which is the requirement for TTF). This also reflects 28.5% of the whole group of patients. Conclusions: Although Imatinib continues to be the preferred first line in treating CML, CP yet it might be more suitable to use a second generation TKI if TFR is planned ahead.
A pancancer analysis of <i>CDK12</i> alterations in Chinese population.
Authors: Luyan Lou, Yanrui Zhang, Huanhuan Liu, Xiayuan Liang, Feng Lou, Shanbo Cao, Huina Wang
Journal: Journal of Clinical Oncology (2022)

e15068 Background: Cyclin-dependent kinases ( CDKs) are key regulators of both cell cycle progression and transcription. Analysis of mutation detection of CDK12 in pan-cancer could contribute to understand the complexity and diversity of genetic alterations present in CDK12 mutant cancers. Herein, we provide a pan-cancer analysis of CDK12 alterations in Chinese population. Methods: Using gene-panel target-capture next generation sequencing, we analyzed 17509 tumor tissue or plasma ctDNA samples from different patients. Testing included analysis of single nucleotide variants, insertions/deletions, fusions and amplifications. CDK12 variants of uncertain significance and synonymous variants excluded. Results: In total, 0.95% (167/17509) of pan-cancer patients harbored CDK12 mutation, and 32 patients carried at least two CDK12 mutations. The most common genetic alteration type was truncating mutations (128, 64%), followed by amplications (53, 26%), missense mutations (9, 5%) and splicing mutations (9, 5%). In our cohort, the highest CDK12 mutation frequency tumor type was prostate cancer(11.30%), followed by breast cancer (3.96%), bladder cacner (3.16%), stomach cancer (1.84%) and colorectal cacner (1.13%). The TCGA pan-cancer cohort confirmed that the CDK12-altered cancer was associated with shorter overall survival (81.11 vs 133.00 mos, p = 5.30×10 −18 ) in prostate cancer. Tumor mutation burdens(TMB) were calculated for 137 samples of all the 167 samples. The median TMB was 7.66 mut/Mb with 38%≥10 mut/Mb and 17%≥20 mut/Mb. including a patient with hypermutated in colorectal cancer(TMB: 88.24 Mut/Mb), harboring three CDK12 mutations. Conclusions: Genomic alterations in CDK12 are widespread among Chinese patients, with alteration rates and alteration types varying by cancer type. We identified prostate cancer as the cancer type with the highest prevalence of CDK12 oncogenic alterations. Additional analyses are ongoing.
Dietary fish oil augments the tumor immune microenvironment in anti-PD-1 treated melanoma.
Authors: Alexander C Chacon, Shuyang Sue Qin, Alexa Melucci, Katherine M. Jackson, Paul R. Burchard, Yatee A. Dave, Rachel Jewell, Brian A. Belt, William Tabayoyong, Peter A. Prieto
Journal: Journal of Clinical Oncology (2022)

e21564 Background: Less than half of metastatic melanoma patients experience objective responses to first line anti-PD-1 immune checkpoint inhibition (αPD-1 ICI). Omega-3 fatty acids in dietary fish oil (FO) shift myeloid and T-cell populations to anti-inflammatory, pro-resolution phenotypes in immunity and cancer. We investigated whether dietary FO supplementation could augment tumor microenvironment (TME) immune profiles and improve ICI response in melanoma. Methods: C57-BL6/J mice were injected with YUMM 1.7 melanoma in the flank. Mice were fed control chow (CTL) or omega-3 rich (FO) chow (10% w/w, 30%kcal/kcal) starting 7 days post tumor implantation. Intraperitoneal αPD1 or IgG2a vehicle were injected q3-4 days starting day 12. To assess the temporal flux of TME immune populations, tumors from mice in analogous experiments were assessed for growth, harvested on day 12, day 22, or day 32, and characterized via flow cytometry. Results: In multiple models, FO decreased YUMM tumor growth vs. CTL by day 32 (&gt; 21% for all models). FO halved tumor associated macrophage content, including M2 macrophages (Arg1+, CD206+, CD68+, F480+), at day 12. Conversely, FO increased M2 macrophages at day 22, leveling even with CTL at day 32. At all three timepoints, FO increased TME monocytes (Ly6C+, Ly6G-). In the T cell compartment, FO decreased TME CD4 and CD8 T cell content (including PD1+ CD4 and PD1+ CD8) at day 12, an effect which was reversed by day 22 (increased CD4 and CD8s vs CTL). FO increased PD-L1+ CD4 T cells and CD8+ T cells, including PD1+ CD8 T cells, on day 32. When fish oil diets were started on day 12 (concurrent with immunotherapy), FO decreased tumor volume, increased monocytes (and PD-L1+ monocytes), and increased CD4 and PD1+ CD8 T cells by day 32, all less significantly than when starting diets 5 days prior to initiation of immunotherapy. All results significant (p &lt; 0.05) by 2-way ANOVA or t-test unless specified. Food eaten, water imbibed, and weight change did not vary between groups. Conclusions: Fish oil impairs in vivo murine melanoma tumor growth with and without αPD-1 ICI. Fish oil modulated myeloid and T cell lineages via delaying M2 macrophage and CD4 / CD8 T-cell appearance in the tumor microenvironment, with concomitant increases in monocytes and key T cell effectors involved in αPD-1 ICI responsiveness by the time decrements in tumor growth were noted. Dietary fish oil may benefit patients with advanced melanoma treated with αPD-1 immunotherapy; further study in humans is warranted.
Application of deep learning models on whole slide images uncover new histological markers related to high-risk malignant pleural mesothelioma.
Authors: Douglas Hartman, Jean-Eudes Le Douget, Ye Ye, Yaming Li, Patrick Sin-Chan, Elodie Pronier, Michael Becich
Journal: Journal of Clinical Oncology (2022)

e13580 Background: Malignant Pleural mesothelioma (MPM) is a highly aggressive cancer of the pleural surface and represents 80-90% of mesothelioma diagnosis. MPM is broadly subclassified into three histological subgroups (epithelioid, sarcomatoid, biphasic), however tissue heterogeneity has resulted in diagnostic challenges and suboptimal patient care. There are currently no specific histological markers of high/low-risk MPM patients, which is critical in predicting patient prognosis. Methods: Owkin developed MesoNet, a deep learning model that predicts overall survival (OS) of MPM patients from whole slide images (WSI) and trained on the French MESOBANK and TCGA cohorts (Courtiol et al, 2019). In this study, we sought to validate MesoNet’s performance on an independent cohort of 127 WSI stained with haematoxylin/eosin from MPM patients collected at the University of Pittsburgh as part of the National Mesothelioma Virtual Bank (funding by U24OH009077). Patient demographics, survival data, expertly curated pathology annotations were also collected. Results: Our analyses showed that MesoNet predicted OS as risk score based on WSI, which validated high-risk MPM patients exhibited poorer OS, as compared to low-risk patients. Analyses on histological subtypes revealed sarcomatoid and biphasic patients were overrepresented in high-risk groups, as compared to epithelioid patients, which correlates with observed OS data. Notably, histological features associated with high-risk patients revealed tumor pleomorphism and anaplastic nuclear features, whereas low-risk tiles appear to be enriched in tumor infiltrating lymphocytes (TILs) with accompanying stromal proliferation and dense fibrosis. Conclusions: Collectively, our studies validate MesoNet performance on an independent cohort and identify new features related to MPM risk groups, which may inform future treatment stratification and personalization of immunotherapies.
Real-world outcomes in patients with <i>KRAS</i> p.G12C mutant advanced non-small cell lung cancer (aNSCLC) treated with docetaxel in second-line or beyond (2L+).
Authors: Hil Hsu, Diana Younan, Gaurav Suri, Victoria M. Chia
Journal: Journal of Clinical Oncology (2022)

e21048 Background: KRAS p.G12C mutation accounts for ̃13% of non-squamous NSCLCs and recently became a druggable target. Prior standard of care (SOC) treatment options have been limited to checkpoint inhibitors and chemotherapies as a monotherapy or combination. This US-based study provides real-world clinicopathological characteristics and outcomes of patients with KRAS p.G12C mutant aNSCLC who received 2L+ docetaxel as SOC. Methods: We conducted a retrospective observational cohort study of adult aNSCLC patients with a KRAS mutation detected via molecular testing as part of real-world care, treated with 2L+ docetaxel in the nationwide, de-identified, EHR-derived Flatiron Health (FH) database and the FH-Foundation Medicine aNSCLC clinicogenomic database between January 1, 2011–March 31, 2021. Clinicopathological and treatment characteristics were described. Median real-world overall survival (rwOS) and progression-free survival (rwPFS) were separately estimated for second, third, and fourth lines of therapy, and as any line 2L+, among eligible patients (i.e., have a minimum of 6 months opportunity for follow-up and not on a clinical trial drug). Analyses were performed for cohorts of patients with KRAS p.G12C mutation and KRAS non-p.G12C mutation, separately. Results: 677 patients with KRAS mutant aNSCLC treated with 2L+ docetaxel were included, of which 295 (44%) had KRAS p.G12C mutation. Among the 295 patients with KRAS p.G12C, mean age (SD) at advanced diagnosis was 65 (+9) years and 59% were female. The majority were White (69%) and had a history of smoking (97%), an initial diagnosis with advanced disease (78%), non-squamous cell carcinoma (96%). In total, 259 patients with KRAS p.G12C mutation were eligible for outcomes assessment. Nearly 69% of these patients initiated docetaxel in 2017 or a later year. Overall, 47% received docetaxel as second line, 35% as third line, 15% as fourth line, and 6% as a fifth or later line, with 4% receiving docetaxel in more than one line. Most (59%) docetaxel regimens were combinations, primarily with ramucirumab, and 41% were monotherapy. Nearly 68% of patients received a PD-1/PD-L1 inhibitor prior to receiving docetaxel. Outcomes are summarized in the Table. Conclusions: Real-world outcomes are poor in patients with KRAS p.G12C mutant aNSCLC treated with docetaxel in 2L or beyond, with a median OS of only 6 months. Patients with aNSCLC harboring a KRAS p.G12C mutation may benefit from available targeted treatment.[Table: see text]
Predictors of response to immune checkpoint inhibitors (ICI) rechallenge post-disease progression in solid tumors: A systematic review and meta-analyses.
Authors: Hassan Mohammed Abushukair, Leen Mohammad Al-Kraimeen, Anwaar Saeed
Journal: Journal of Clinical Oncology (2022)

2612 Background: Rechallenge with the same or different ICI has been proposed as a second line option in patients who progress on an initial ICI course. Considering rechallenge risks of limited benefit and further toxicity, identifying predictors for patients benefiting from rechallenge would provide much needed guidance for practice. We present a systematic review and meta-analyses of response predictors to ICI rechallenge after disease progression in solid tumors. Methods: A systematic search of PubMed, Cochrane database and ASCO meeting library was done for studies published up to Jan 2022 evaluating the efficacy of ICI rechallenge in patients with advanced solid tumors after disease progression on initial ICI. Predictors of interest included duration of the initial ICI course using a cutoff point of 6 months, and best overall response (BOR) to initial ICI: stratified into responders (complete or partial response or stable disease) and non-responders (progressive disease). Odds ratios (OR) for ICI rechallenge response were calculated &amp; pooled in reference to initial ICI duration and its BOR using the fixed effects model. ORs with a 95% confidence interval [CI] not overlapping the null value (1) were considered statistically significant. Results: A total of 56 studies reporting on ICI rechallenge upon progression, comprising 3579 patients, of which 31 studies have switched their second ICI regimen. Initial ICI was anti-PD-1 in 37 studies, anti-CTLA-4 in 14 studies, and anti-PD-L1 in 10 studies. Involved solid cancers included melanoma (n = 30), NSCLC (n = 15), RCC (n = 6), and others (n = 5). Pooled objective response rate for rechallenge was 18.4% ([15.4-21.4], I 2 = 84.6%), with the highest being among melanoma patients (21.2% [17.2-25.2], I 2 = 83.4%). For BOR, no significant difference was found for the entire cohort (OR = 1.34 [0.86 - 2.09], I 2 = 27.1%). In melanoma studies, response to ICI rechallenge was significantly higher in patients responding to the initial ICI prior to progression (OR = 1.87 [1.03-3.39], I 2 = 24.5%). For treatment duration, there was no difference in the entire cohort concerning ICI rechallenge (OR = 1.54 [0.86-2.75], I 2 = 14.2%), yet melanoma patients showed a significant difference favoring those who had longer response durations on initial ICI (OR = 2.05 [1.01-4.16], I 2 = 0.0%). Conclusions: Response to rechallenge in advanced melanoma patients was more common in initial ICI responders with a longer course duration ( &gt; 6 months). More homogeneous studies are needed to validate our findings and investigate other potential markers for rechallenge such as PD-L1 status &amp; mutational burden. [Table: see text]